title: A pilot study of human interferon beta gene therapy for patients with advanced melanoma by in vivo transduction using cationic liposomes.
abstract: BACKGROUND
  Cationic liposomes containing the human interferon beta (HuIFNbeta) gene (IAB-1) was used for the clinical trial for glioma patients. HuIFNbeta gene therapy showed much higher anti-tumor activity compared with the administration of HuIFNbeta protein for melanoma. These results suggest that HuIFNbeta gene therapy is an attractive strategy for the treatment of melanoma.
  
  
  METHODS
  Stage IV or III melanoma patients with cutaneous or subcutaneous metastatic lesions were enrolled in this pilot study. IAB-1 was dissolved by sterile PBS at a concentration of 30 microg DNA/ml and was injected into cutaneous or subcutaneous metastatic nodules three times a week for 2 weeks and the effect on the injected and non-injected metastatic lesions was evaluated.
  
  
  RESULTS
  Clinical responses were as follows (five patients): mixed response (MR) and no change in each one patient, and progressive disease in three patients. In the MR patient, the IAB-1 injected lesion disappeared clinically and histopathologically and one-half of IAB-1 non-injected skin metastases were transiently inflamed and mostly regressed. In the responded non-injected lesions of this patient, histopathologically, infiltration of CD4 positive T cells was observed around the melanoma cells in the dermis, which expressed the HLA-Class II antigen. Adverse events due to this gene therapy were not recognized in any of the patients.
  
  
  CONCLUSIONS
  The efficacy of this gene therapy was generally insufficient; however, some immunological responses were recognized in one patient. No adverse events were observed. HuIFNbeta gene therapy could be an attractive strategy for treatment of a variety of malignancies, including melanoma, though some modifications should be required.
authors.affiliation: Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan. climatsu@shinshu-u.ac.jp
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kubo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murata
authors.forename: Hisashi
authors.initials: H
authors.lastname: Uhara
authors.forename: Minoru
authors.initials: M
authors.lastname: Takata
authors.forename: Shinichi
authors.initials: S
authors.lastname: Shibata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasue
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sakakibara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tomita
authors.forename: Toshiro
authors.initials: T
authors.lastname: Kageshita
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Masaaki
authors.initials: M
authors.lastname: Mizuno
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshida
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saida
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002412:Cations; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage* / Q000235:genetics*; D008081:Liposomes; D008297:Male; D008545:Melanoma / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D010865:Pilot Projects; D010957:Plasmids; D012878:Skin Neoplasms / Q000473:pathology / Q000628:therapy*; D014161:Transduction, Genetic / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D008081:Liposomes; D016899:Interferon-beta